AB0645 Nintedanib in treatment of pulmonary fibrosis secondary to Connective Tissue Disease:
Authors: A. Laria, A. M. Lurati, D. Mazzocchi, K. Re, M. G. Marrazza, E. Zaccara, D. Bompane, A. Tamburello, L. Castelnovo, F. Bini, P. M. Faggioli, A. Mazzone
Journal: Annals of the Rheumatic Diseases (2022)

Background Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and other Rheumatic Diseases, and is one of the major causes of mortality. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and anti-inflammatory effects in preclinical models of systemic sclerosis and ILD. Objectives To evaluate efficacy and safety of Nintedanib in pulmonary fibrosis secondary to Connective Tissue Disease. Methods Ten patients with pulmonary fibrosis secondary to Connective Tissue Disease treated with Nintedanib were monitored at baseline, 6 and/or 12 months, with clinical assessment, chest CT scan and/or pulmonary function testing (PFT) with assessment of the diffusing capacity for CO (DLCO). 8/10 patients had a diagnosis of Progressive Systemic Sclerosis, while the remaining ones had Polydermatomyositis and Mixed Connectivitis. All patients were dyspnoic at baseline and presented with dry cough. All patients had pulmonary fibrosis according to high-resolution chest CT scan. All patients had been treated with at least one csDMARD or bDMARD (cyclophosphamide, azathioprine, cyclosporine, rituximab, tocilizumab), prior to receiving nintedanib. At baseline 2/10 patients were treated with Nintedanib monotherapy, 7/10 were in combination therapy with Mycophenolate, 1 patient received a combination therapy with cyclosporine. Results Compared to baseline values, 4/7 patients showed stationarity of the respiratory function parameters (DLCO), in 2/7 patients it was observed a significant improvement of the DLCO (with a change of 15%) while in only 1 patient there was a worsening over time. FVC remained stable over time except in 1 patient who got a significant improvement. In 5/9 patients cough improved (unchanged in the rest of patients). Dyspnea (NYHA scale) improved in 6/9 patients, remained stationary in 2/6 patients and became worse in 1 patient. 8/9 patients had a stable chest CT at 6 and / or 12 months, while only 1 patient witnessed a further worsening of the fibrosis. 50% of the patients showed good gastrointestinal tolerance to the full dose of nintedaninb. The other half had the dose reduced in order to improve gastrointestinal symptoms. Conclusion Our data show that patients with ILD associated with Rheumatic Diseases treated with nintedanib had a clinical benefit over dyspnea and cough symptoms and a stabilization of radiological findings 12 months after starting the treatment. Also, respiratory function parameters remained stable over time. Gastrointestinal adverse events, including diarrhea, were common in these patients, but therapeutic dose adjustment led to fast symptoms resolution and good tolerance. References [1]Kristin B Highland, Oliver Distler, Masataka Kuwana, Yannick Allanore, Shervin Assassi, Arata Azuma, Arnaud Bourdin, Christopher P Denton, Jörg H W Distler, Anna Maria Hoffmann-Vold, Dinesh Khanna, Maureen D Mayes, Ganesh Raghu, Madelon C Vonk, Martina Gahlemann, Emmanuelle Clerisme-Beaty, Mannaig Girard, Susanne Stowasser, Donald Zoz, Toby M Maher, SENSCIS trial investigators. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial. Lancet Respir Med. 2021 Jan;9(1):96-106. [2]Oliver Distler, Kristin B Highland, Martina Gahlemann, Arata Azuma, Aryeh Fischer, Maureen D Mayes, Ganesh Raghu, Wiebke Sauter, Mannaig Girard, Margarida Alves, Emmanuelle Clerisme-Beaty, Susanne Stowasser, Kay Tetzlaff, Masataka Kuwana, Toby M Maher, SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528. Disclosure of Interests None declared